Barbiturates extraction

Figure 11.19 SPME-CE analysis of urine samples (a) blank urine (a) directly injected and extracted for (b) 5 (c) 10 and (d) 30 min (b) Urine spiked with barbiturates, extracted for (e) 30 and (f, g) 5 min. Peak identification is as follows 1, pentobaitibal 2, butabarbital 3, secobarbital 4, amobarbital 5, aprobarbital 6, mephobarbital 7, butalbital 8, thiopental. Concenti ations used are 0.15-1.0 ppm (e, f) and 0.05-0.3 ppm (g). Reprinted from Analytical Chemistry, 69, S. Li and S. G. Weber, Determination of barbiturates by solid-phase microexti action and capillary electrophoresis, pp. 1217-1222, copyright 1997, with permission from the American Chemical Society.

Therefore, these reactions constitute a means to distinguish both sorts of barbiturs. This result must be connected to Denigds reaction used in analytical toxicology in order to search for barbiturics extracted in acidic medium. Deniges reagent is mercuric sulfate in a mixture of sulfuric and acetic acids ... 

Capsules of Amylobarbitone Sodium, J5.P., Tablets of Amylobar-bitone Sodium, P.P. Tablets of Barbitone Sodium, P.P., Tablets of Pentobarbitone Sodium, P.P., and Tablets of Phenobarbitone Sodium, P.P. The tablets are liable to absorb carbon dioxide rapidly on exposure and liberate a considerable proportion of free barbiturate, extractable with ether from the powdered material. 

The analysis of clinical samples is often complicated by the complexity of the sample matrix, which may contribute a significant background absorption at the desired wavelength. The determination of serum barbiturates provides one example of how this problem is overcome. The barbiturates are extracted from a sample of serum with CHCI3, and extracted from the CHCI3 into 0.45 M NaOH (pH 13). The absorbance of the aqueous extract is measured at 260 nm and includes contributions from the barbiturates as well as other components extracted from the serum sample. The pH of the sample is then lowered to approximately 10 by adding NH4CI, and the absorbance remeasured. Since the barbiturates do not absorb at this pH, the absorbance at pH 10 is used to correct the absorbance at pH 13 thus... 

The concentration of the barbiturate barbital in a blood sample was determined by extracting 3.00 mL of the blood with 15 mL of CHCI3. The chloroform, which now contains the barbital, is then extracted with 10.0 mL of 0.045 M NaOH (pH = 13). A 3.00-mL sample of the aqueous extract is placed in a 1.00-cm cell, and an absorbance of 0.115 is measured. 

Pentobarbital (5-ethyl-5-r-methylbutyl barbituric acid. Nembutal) [76-74-4] M 226.4, m 127 (dec), pKEst(i) 8.0, pKEst(2) 12.7. Soln of the sodium salt in 10% HCl was prepared and the acid was extracted by addition of ether. Then purified by repeated crystn from CHCI3. [Bucket and Sandorfy J Phys Chem 88 3274 1984.]... 

The use of SPME for CE has not (yet) been studied widely. Li and Weber (170) reported an off-line SPME-CE approach for the determination of barbiturates in urine and serum, utilizing a sorbent of plasticized PVC coated around a stainless steel rod. Eor extraction, the coated rod was inserted for 4 min in a Teflon tube containing 50 p.1 of sample, and next the rod was repeatedly desorbed in another Teflon tube which each time contained 5 p.1 of desorption solution. This solution was transferred to an injection vial and an aliquot was injected into the CE system (Eigure 11.19). The extraction procedure appeared to be selective and effectively allowed the handling of very small samples. 

Preparation of 1-Methyl-5-Allyl-5-( 1-Methyl-2-Pentynyl) Barbituric Acid A solution of 23.8 g of sodium in 360 ml of absolute alcohol was prepared and thereto were added 38.3 g of methyl urea and 96.8 g of diethyl allyl (1-methyl-2-pentynyl) malonate. The mixture was refluxed for about 20 hours, cooled, and the ethanol was removed by distillation in vacuo. The residue was dissolved in about 300 ml of water and the aqueous solution was washed with ether, and the washings were discarded. The aqueous solution was then acidified with acetic acid, and extracted with three 150 ml of portions of ether. 

The combined ether extracts were washed with 5% aqueous sodium bicarbonate solution, dried over anhydrous sodium sulfate, and fractionally distilled in vacuo. The fraction boiling at about 145° to 150°C at the pressure of 0.5 mm of mercury, weighing 61 g and consisting of 1-methyl-5-allyl-5-(1-methyl-2-pentynyl) barbituric acid, was collected. The only distillate was substantially pure, and could be used as such In pharmaceutical preparation or a salt could be prepared therefrom according to the procedures disclosed hereinafter. On standing, the oil crystallized. The crystalline 1-methyl-5-allyl-5-( 1-methyl-2-pentynyl) barbituric acid melted at about 60° to 64°C after recrystallization from dilute ethanol. 

Preparation of Sodium 1-Methyl-5-Allyl-5-(1-Methyl-2-Pentynyl) Barbiturate A solution of 61 g of 1-methyl-5-allyl-5-(1-methyl-2-pentynyl) barbituric acid in 100 ml of ether was extracted with 465 ml of 2% aqueous sodium hydroxide solution. The aqueous extract was washed with successive 75 ml and 50 ml portions of ether. The pH of the aqueous solution was adjusted to 11.7, using 5% aqueous sodium hydroxide solution. 5 g of decolorizing carbon were added to the solution with stirring the mixture was permitted to stand for 20 minutes at room temperature, and the carbon was removed by filtration. A solution containing 4 g of sodium carbonate in 25 ml of water was added to the aqueous solution, and the mixture was filtered sterile through a porcelain filter candle of 02 porosity into sterile bottles. The aqueous solution was then dried from the frozen state, whereupon a sterile residue of sodium 1-methyl-5-allyl-5-(1-methyl-2-pentynyl) barbiturate, weighing about 62 g was obtained. 

Heating MethElute (Pierce 49300X) with drug-containing extracts from body fluids gives quantitative methylation of barbiturates, sedatives, and so on. Follow the procedure provided by Pierce Chemical Company using the MethElute reagent. 

Occupational air (NIOSH Method 6010) Collection of breathing zone air samples on adsorbent extraction with water treatment with barbituric acid/ pyridine reagent Spectrophotometry (HCN) 1 pg CNb -100% NIOSH 1989b... 

Barbiturates represent a class of sedative and hypnotic drugs employed extensively in medicine. RIA provides a rapid, sensitive specific and reliable means for their determination in plasma levels upto 5 ng without indulging in any type of extraction, filtration or evaporation as required for other conventional analytical methods. ... 

Paradoxically, catnip fed to mice had stimulant effects, with increased rearing, locomotion, and stereotypical behavior, increased susceptibility to chemically induced (picrotoxin and strychnine) seizures, and decreased sleeping time after barbiturate administration (Massoco et al. 1995). The LD50 for nepetalactone in mice was reported to be quite high at 1300 mg/kg (Harney et al. 1978). In chicks, an a cohol extract of catnip had biphasic effects, where low to moderate doses (25-1800 mg/kg) produced sedative effects, while higher doses (>2 g/kg) had less sedative and perhaps stimulant effects (Sherry and Hunter 1979). Humans have reported sedative effects of catnip, and one accidental ingestion by a young child reportedly produced sedative effects (Osterhoudt et al. 1997). 

Gentian (Oentiono lutea) Uses t Appetite, treat digestive disorders such as colitis, IBS, flatulence Actions Chemical components stimulate digestive juices Available forms Liq extract 2-4g PO OD, tine 1-3 g PO OD, dried root 2-4 g PO OD Contra Do not use PRO, lactation, HTN Notes/SE N/V, HA Interactions t CNS sedation W/ barbiturates, benzodiaz ines, EtOH if extract/tinc contains alcohol -1- absorption OF Fe salts EMS many preps contain up to 60% EtOH... 

There appears to be little difference between benzodiazepines and kava extract in anxiolytic activity. However, kava extracts seem to have fewer side effects. Two studies with more than 3000 patients each found unwanted events in about 2% of patients during treatment with kava extract. The more frequently reported side effects were gastrointestinal complaints, allergic skin reactions, headache, and photosensitivity (Pittler and Ernst, 2000). There have been isolated reports of hepatotoxicity and acute liver failure (Escher et ah, 2001). Kava may potentiate the sedative effects of other medications including barbiturates and benzodiazepines. Kava can also cause behavioral disinhibition in a minority of individuals, including children. The most common problem, which is usually associated with persistent and excessive usage, is a scaly skin rash called kava dermopathy, which is reversible. 

Tatsumi K, Fukushima M, Shirasaka T et al. Inhibitory effects of pyrimidine, barbituric acid, and pyridine derivatives on 5-fluorouracil degradation in rat liver extracts. Jpn J Cancer Res 1987 78 ... 

Most drugs used in anaesthesia are metabolised in the liver by phase I reactions, mediated by cytochrome P-450 enzymes. These are susceptible to destruction by cirrhosis, so that the biotransformation of drugs, such as opioids (except morphine), benzodiazepines, barbiturates, and inhalational agents, may be markedly altered in severe liver disease. These enzymes are found in the centrilobular areas, which are more prone to hypoxia. In contrast, the enzymes responsible for phase II reactions, found predominantly in the peripheral areas, often function normally even in advanced disease. The disposition of benzodiazepines that are eliminated primarily by glucuronidation, e.g. lorazepam and oxazepam, are unaffected by chronic liver disease. For drugs with low hepatic extraction, advanced hepatocytic dysfunction decreases phase I and II biotransformation with a reduced clearance and prolongation of the elimination half-life. This is often partially offset by an increased free fraction due to decreased protein binding. 

Barbiturates are referred to as sedative-hypnotics. These drugs will induce sleep which can lead to even deeper sedation (hypnosis) and can cause a fatal depression of the RAS affecting the respiratory system. The sleep which is encountered does not have the normal cycles of slow wave and rapid eye movement activity, so it is not always restful. However, these agents prove to be useful in anesthesia for both short and longer durations of time. Many of you may have been given thiopental prior to wisdom tooth extraction. Thiopental "wears off quickly and so the actual anesthetic for the time of the extraction is usually nitrous oxide. 

Valerian Valeriana officinalis) The roots of this plant are dried to produce a potent extract that induces sleepiness and helps treat insomnia. Like lavender, it depresses the activity of the central nervous system in a fashion similar to stronger prescription tranquilizers such as benzodiazepines and barbiturates, but without the dulling or hangover effects the next day or impairing the ability to drive a car. 

This technique can be also applied when the water-miscible acetonitrile is added to the serum sample for extracting the analytes. Following the addition of acetonitrile, the solution is saturated with potassium chloride so that the water and acetonitrile phases separate and derivatization is performed in the acetonitrile layer. Such alkylating procedures have been applied for prechromatographic derivatization of various drug residues with carboxylic groups, including penicillins (252) and barbiturates (253). 

Separation selectivity was demonstrated by extraction of salicylic acid from pH 2 solutions in the presence of a 60-fold excess of ethanol and sixfold excesses of barbituric acid and caffeine. No measurable interference was observed. Experiments showed that the principal selectivity is in the extraction rather than the back extraction step. This finding indicated that the polar and/or ionic nature of these interferences prevents retention by polymer. Preconcentration of analyte was examined by means of extraction from a flowing stream and back extraction into a minimum volume. The extractor tube length was 4.3 m, and the sample was 10 mL of 1 mM oxine with an extraction time of 2.0 min. The back extractant was 80 pL of 0.2 M NaOH. A sevenfold increase in concentration was observed. Enhanced preconcentration can be expected with smaller tubing diameter-to-length ratios, larger sample volumes, and repetitive use of back extractant. 

Barbiturates (96) and nitrazepan (97) have been methylated by the extractive alkylation procedure, using ICH3.155,156... 

As with most other drugs, no single extraction method will suffice for removing any barbiturate from any biological sample, and recovery will depend on technique. Generally, multiple solvent extraction under different pH conditions has been used. 

Street (34) developed an "on column" derivative formation technique using N,0-bis (trimethylsilyl) acetamide (BSA). A few microliters of BSA are drawn into a 10-yl syringe followed by several microliters of extract to be chromatographed. The whole is injected onto the column with the resultant formation of and separation of the derivatives. This procedure is recommended for the formation of methyl and trimethylsilyl derivatives in qualitative determinations, and the separation of nonderivatized barbiturates for quantification procedures. 

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